Cancer is not a risk factor for severe COVID-19 in children, except in patients with recent allogeneic hematopoietic stem cell transplantation or comorbidities.

The EPICO (Spanish general registry of COVID-19 in children)-SEHOP (Spanish Society of Pediatric Hematology and Oncology) platform gathers data from children with SARS-CoV-2 in Spain, allowing comparison between children with cancer or allogeneic hematopoietic stem cell transplantation (alloHSCT) and those without. The infection is milder in the cancer/alloHSCT group than in children without comorbidities (7.1% vs. 14.7%), except in children with recent alloHSCT (less than 300 days), of which 35.7% experienced severe COVID-19. These data have been shared with the SEHOP members to support treatment and isolation policies akin to those for children without cancer, except for those with recent alloHSCT or additional comorbidities. This highlights the collaborative registries potential in managing pandemic emergencies.

Prevalence and associated factors of iron deficiency in Spanish children aged 1 to 11 years.

Iron deficiency (ID) is the most common nutritional deficiency affecting children worldwide. Most traditional laboratory parameters to assess ID can be altered by infections or other inflammatory states, including obesity. The aims of this study were to determine the prevalence of ID in healthy children and to analyse associated factors, avoiding potential confounding factors through the use of serum transferrin receptor (sTfR), reticulocyte haemoglobin content and sTfR/log ferritin index. A cross-sectional population-based study was conducted on 951 children aged 1 to 11 years in Almería (Spain). ID was detected in 7.7% of children and iron deficiency anaemia in 0.9%. Multivariate analysis identified the following as independent risk factors: age under 5 years (OR: 2.2, 95% CI: 1.35-3.6); excessive consumption of cow's milk and dairy products (OR: 1.87, 95% CI: 1.13-3.1); and insufficient consumption of vegetables (OR: 2.7, 95% CI: 1.2-6.1).Conclusions: Using a combination of iron status parameters with greater discriminatory power than classical measures, this study detected a considerable iron deficiency prevalence in Spanish children. Younger children and specific dietary habits exhibit a particular risk for ID, so special attention should be paid to this population. What is Known: • Iron deficiency remains the most prevalent nutritional deficit worldwide, and children aged under 3 years are the most vulnerable to this condition. • Accurate assessment of iron status, based on a combination of biochemical indicators, can often be complicated. What is New: • Iron deficiency continues to present a health problem in Spanish children aged 1 to 11 years, considering the serum transferrin receptor and reticulocyte haemoglobin content for diagnosis. • Excessive consumption of dairy products and low consumption of vegetables are independent risk factors for iron deficiency.

Distinct Laboratory and Clinical Features of Secondary Hemophagocytic Lymphohistiocytosis in Pediatric Visceral Leishmaniasis: A Retrospective Analysis of 127 Children in Andalusia, Spain (2004-2019).

BACKGROUND: Visceral leishmaniasis (VL) is an endemic in Southern Europe. However, details regarding disease burden, clinical presentations, laboratory markers, management and outcome in children are scarce. METHODS: Medical records of children (<14 years) admitted with VL to 10 pediatric units in Andalusia (2004-2019) were retrospectively reviewed. VL diagnosis was based on clinical presentation, serology, microscopy and molecular methods. Diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) was established using the hemophagocytic lymphohistiocytosis-2004 criteria. RESULTS: A total of 127 patients were identified. Median age was 14.5 months; the main clinical presentations were fever and splenomegaly (95.3% each). Cytopenias were the most common laboratory abnormalities. Diagnostics as well as treatment regimens varied over time and the participating centers. Liposomal amphotericin B was prescribed in 97.6%; relapses as well as adverse events were rarely observed (3.1% each). Thirty-seven patients, diagnosed with sHLH required longer hospital admission (P = 0.001), an increased number of platelet (P < 0.006) and red blood cell (P = 0.0001) transfusions and pediatric intensive care unit admission (P = 0.007). Monocytopenia (P = 0.011) and high C-reactive protein levels (P = 0.031), variables not included in the hemophagocytic lymphohistiocytosis-2004 criteria, were associated with sHLH. One patient deceased in the context of the Leishmania infection. CONCLUSIONS: We report data on the largest pediatric VL cohort from Europe, commonly associated with sHLH. Raised C-reactive protein levels and monocytopenia appear to be associated with sHLH. The latter may help to identify these patients and to guide decisions regarding need of additional supportive clinical care and immunomodulatory therapies. The observed high rate of heterogeneity in terms of diagnosis and management warrants the establishment of appropriate guidelines.

Status of folate in healthy children in Almeria.

The objective of this study is to establish reference values for folic acid in a healthy population of children aged 4-11 years and to examine related epidemiological, dietary and analytical factors. A cross-sectional study of 658 healthy children aged 4-11 years was made. Epidemiological, socioeconomic and dietary variables were analysed, the BMI Z-score was obtained, levels of serum folate and serum vitamin B12 were determined and haematological, iron status and erythropoietic activity parameters were examined. The study data were analysed by non-parametric tests and linear multiple regression. The mean folate value was 8.6 ± 4.6 ng/mL (95% reference interval: 2.8-20 ng/mL). A level < 3 ng/mL (5th percentile) was considered as folate deficiency (4.6% of subjects). No child reported symptoms related to this deficiency. Folate values were significantly lower with age (p < 0.01), low NSE and low parental educational level (p: 0.0001). No relationship was found between folates and the analytical variables. According to multivariate linear regression, the variables significantly associated with serum folate were age, socioeconomic level and vitamin B12.Conclusions: Serum folate levels in healthy school children are described. Age, socioeconomic level and serum vitamin B12 are factors associated with folate status. Specific cut-off values for a paediatric population should be defined. What is Known: • Folic acid is an essential micronutrient for optimal growth and development; its deficit is associated with adverse health effects. • The studies on their status and deficit are not comparable due to a lack of agreement on appropriate indicators and reference values. What is New: • This study reports the levels of serum folate in a large population of healthy schoolchildren, with strict inclusion criteria in a developed country and identifies the associated sociodemographic, dietary and analytical (vitamin B12, iron parameters and erythropoietic activity) factors, avoiding potential confusion.

Relationship between Obesity and Iron Deficiency in Healthy Adolescents.

The relationship between overweight/obesity (excess of weight [EW]) and iron deficiency (ID) is not well defined. Objective: To analyze the relationship between EW and ID in healthy adolescents, assessing the contribution of new diagnostic measures of iron status and erythropoietic activity. Method: A cross-sectional study was made of 405 healthy adolescents, 12-16 years of age. A total of 289 were normal weight (NW) and 116 were otherwise healthy EW. Epidemiological, socioeconomic, diet, BMI Z-score, CRP (C-reactive protein), hematological, iron status, and erythropoietic activity parameters were measured. Statistical tests were Student's, analysis of variance (ANOVA), Chi-square, Pearson's correlation, and odds ratio. Results: ID prevalence in the EW group was 22.6% vs. 29.5% in the NW group (p: 0.3). Greater body weight was associated with lower reticulocyte hemoglobin content (CHr) (NW: 31.3 ± 1.7 pg vs. OW: 30.2 ± 1.7 pg, p: 0.007) and greater CRP (NW: 0.1 ± 0.2 mg/dL vs. OW: 0.2 ± 0.18 mg/dL, p < 0.001), leukocytes (NW: 6.69 ± 1.57 × 103/L vs. OW: 7.43 ± 1.63 × 103/L, p < 0.02), platelets (NW: 265.6 ± 58.9 × 103/L vs. OW: 291.8 ± 54.4 × 103/L, p < 0.002), ferritin (NW: 32.1 ± 17.9 ng/mL vs. OW: 42.8 ± 20.3 ng/mL, p: 0.01), serum transferrin receptor (sTfR) (NW: 1.39 ± 0.4 mg/L vs. OW: 1.73 ± 0.45 mg/L, p: 0.008), sTfR-F index (sTfR/log Ferritin) (NW: 1.06 ± 0.7 vs. OW: 1.33 ± 0.85, p: 0.036) and reticulocyte count (NW: 54.2 ± 18 × 103/L vs. OW: 65.4 ± 24.2 × 103/L, p: 0.003). A positive correlation was observed between the BMI Z-score and CRP, ferritin, sTfR, leukocytes, platelets, and reticulocyte count, and a negative one between the BMI Z-score and CHr and medium corpuscular volume. Conclusions: The prevalence of ID in otherwise healthy EW adolescents was no higher than in NW. The effect of obesity on iron status was low. The findings reveal the concomitant low-grade inflammation, and probably the effect of adiposity on erythropoietic activity. Specific cutoff values for ID in adolescents with OW need to be defined.

Prevalence of iron deficiency and related factors in Spanish adolescents.

Iron deficiency anaemia continues to be the world's most important cause of years lived with disability in children and adolescents. Assessment of iron deficiency traditionally depended on laboratory parameters that may be modified by inflammation states, including obesity, which is nowadays a current condition in adolescent population of high-income countries. The present study ascertains the prevalence of iron deficiency and its related factors in adolescents, using the serum transferrin receptor and the reticulocyte haemoglobin content, in order to avoid this confusing effect of classical parameters. A cross-sectional study was conducted on a population-based representative sample for teenagers in Almería (Spain), of 405 subjects aged 12 to 16 years. Iron deficiency was present in 13.3% of adolescents, but iron deficiency anaemia only in 1.2%. Multivariate logistic regression analyses showed that being part of an immigrant family, a low iron bioavailability diet, meat consumption below four times a week and fish consumption below twice a week, were independent risk factors for iron deficiency.Conclusion: This study provides an estimate iron deficiency prevalence of 13.3% in Spanish healthy adolescents, avoiding potential confounding factors through the use of new iron status parameters, based on a wide representative sample of adolescents from the city of Almería. What is Known: • For children and adolescents, iron deficiency anaemia continues to be the world's most important cause of years lived with disability. • Assessment of iron deficiency has traditionally depended on laboratory parameters that may be modified by inflammatory states, including obesity. What is New: • Iron deficiency prevalence and their related factors were analysed in Spanish adolescents, avoiding potential confounding factors through the use of sTfR and CHr. • Being part of an immigrant family and consuming a low iron bioavailability diet are independent risk factors for iron deficiency.

The usefulness of reticulocyte haemoglobin content, serum transferrin receptor and the sTfR-ferritin index to identify iron deficiency in healthy children aged 1-16 years.

This cross-sectional study, conducted on a population-based representative sample, evaluates the usefulness of reticulocyte haemoglobin content (CHr), serum transferrin receptor (sTfR) and sTfR/log ferritin (sTfR-F index) to recognise iron deficiency (ID) without anaemia, provides specific cut-off points for age and gender, and proposes a new definition of ID. A total of 1239 healthy children and adolescents aged 1-16 years were included. Complete blood count, iron biomarkers, erythropoietin, C-reactive protein, CHr, sTfR, and sTfR-F index were determined. ROC curves were obtained and sensitivity, specificity, predictive values, likelihood ratios, and accuracy for each specific cut-off points were calculated. Seventy-three had ID without anaemia. Area under the curve for sTfR-F index, sTfR and CHr were 0.97 (CI95% 0.95-0.99), 0.87 (CI95% 0.82-0.92) and 0.68 (CI95% 0.61-0.74), respectively. The following cut-off points defined ID: sTfR-F Index > 1.5 (1-5 years and 12-16 years boys) and > 1.4 (6-11 years and 12-16 years girls); sTfR (mg/L) > 1.9 (1-5 years), > 1.8 (6-11 years), > 1.75 (12-16 years girls) and > 1.95 (12-16 years boys); and CHr (pg) < 27 (1-5 years) and < 28.5 (6-16 years).Conclusions: CHr, sTfR and the sTfR-F index are useful parameters to discriminate ID without anaemia in children and adolescents, and specific cut-off values have been established. The combination of these new markers offers an alternative definition of ID with suitable discriminatory power. What is Known: • In adults, reticulocyte haemoglobin content (CHr), serum transferrin receptor (sTfR) and sTfR/log ferritin index (sTfR-F index) have been evaluated and recognised as reliable indicators of iron deficiency (ID). • Clinical manifestations of ID may be present in stages prior to anaemia, and the diagnosis of ID without anaemia continues to pose problems. What is New: • CHr, sTfR and the sTfR-F index are useful parameters in diagnosis of ID in childhood and adolescence when anaemia is not present. • We propose a new strategy for the diagnosis of ID in childhood and adolescence, based on the combination of these measures, which offer greater discriminatory power than the classical parameters.

Reference Values of Reticulocyte Hemoglobin Content in Healthy Adolescents.

Assessing iron status in a pediatric population is not easy, as it is based on parameters that undergo physiological variations in childhood and adolescence. Analysis of the reticulocyte hemoglobin content (CHr) to screen for iron deficiency may increase the accuracy of diagnosis, but, to date, reference values in healthy adolescents have not been adequately determined. A cross-sectional study was conducted on a population-based representative sample in the city of Almería (Spain), with 253 healthy non-iron-deficient (ID) subjects, aged 12 to 16 years. The mean CHr value was 31.6±1.3 pg. The CHr 2.5 percentile was 28.7 pg. There were no significant differences as regards age or sex. In the multivariate linear regression analysis, sex did not influence the variability of CHr, but it was related to age. CHr was influenced by hemoglobin and the Mentzer index, as well as by functional iron indicators such as erythrocyte protoporphyrin and serum transferrin receptor. These independent variables predicted two thirds of the variability in healthy adolescents (R=0.55). This study provides CHr reference ranges in healthy adolescents for use in clinical practice for the early detection of ID states. In populations with similar sociodemographic characteristics, values above the 2.5 percentile rule out ID, as values under the 2.5 percentile could be suggestive of functional ID.

Reference Values of Reticulocyte Hemoglobin Content and Their Relation With Other Indicators of Iron Status in Healthy Children.

Reticulocyte hemoglobin content (CHr) is considered an indicator of functional iron deficiency, but is understudied in children. The goals of this study are to determine the reference intervals for CHr in healthy children, and their relation with iron parameters, erythropoiesis, and individual conditions. A total of 902 children without iron deficiency, aged 1 to 11 years were analyzed in a cross-sectional study. Besides a physical examination of the subjects and a questionnaire completed by their parents, the complete blood count, serum transferrin receptor, ferritin, transferrin saturation, erythrocyte protoporphyrin, serum erythropoietin, C-reactive protein, and CHr levels were measured. Changes in CHr, iron status, and erythropoiesis at different age intervals were analyzed and linear multiple regression was used to identify the factors that determine CHr variability. Mean value obtained for CHr was 30.9±1.8 pg (P2.5-P97.5: 26.9 to 34.3 pg), but the influence of age on CHr (the values increased with age) and on the iron parameters justified the establishment of different reference ranges. In addition to age, nutritional status, hematologic measurements, reticulocytes, transferrin saturation, and erythrocyte protoporphyrin accounted for 39% of CHr variability.

Reference values of serum transferrin receptor (sTfR) and sTfR/log ferritin index in healthy children.

ABSTARCT The aims of this study were to determine appropriate reference ranges for serum transferrin receptor (sTfR) and sTfR/log ferritin (sTfR-F index) in healthy children and their relationship with iron parameters, erythropoiesis, and other conditions presented by the subject. A total of 902 children with normal iron status, aged 1-11 years, were included in a cross-sectional study. A physical examination was conducted and z-score of body mass index (zBMI) obtained. Complete blood count, iron biomarkers, erythropoietin, C-reactive protein, sTfR, and sTfR/log ferritin were determined. Linear multiple regression was applied to identify the factors that determined sTfR and sTfR-F index variability. Mean values for sTfR and sTfR-F index were 1.22 ± 0.28 mg/L (95% confidence interval [CI]: 1.2-1.23) and 0.87 ± 0.25 (95% CI: 0.85-0.88). The reference intervals (2.5th to 97.5th percentiles [P2.5-P97.5]) were 0.78-1.9 mg/L and 0.49-1.46, respectively. sTfR and sTfR-F values decreased with age (P <.03 and P <.0001, respectively). No changes were observed with sex. Changes in sTfR and sTfR-F index were consistent with ferritin and erythropoietin variations. Iron biomarkers, erythropoietin, and zBMI predicted 19% and 18.1% of the sTfR and sTfR-F index variability. The results provide reference ranges for sTfR and sTfR-F index in healthy children for clinical use in the assessment of body iron status. Both biomarkers are predicted by iron parameters, erythropoietin, and zBMI.

Reference values of serum transferrin receptor and sTfR/log ferritin index in healthy adolescents.

Adolescence is a period of increased iron requirements, which impact on iron status. The purpose of this research is to determine the reference intervals for serum transferrin receptor (sTfR) and sTfR/log ferritin index (sTfR-F index) in healthy adolescents, and their relation with iron parameters and erythropoiesis. A total of 253 healthy adolescents without overweight, aged 12 to 16 years, were selected in a cross-sectional study. Hemoglobin, red cell indices, reticulocyte hemoglobin content (rHb), reticulocytes, ferritin, transferrin saturation, erythrocyte protoporphirin, erythropoietin, C-reactive protein, sTfR, and sTfR-F index were measured. Changes in erythropoiesis and iron status in the age interval were observed and analyzed, and linear multiple regression was applied to identify the factors that determine the variability of sTfR and sTfR-F index. Mean values for sTfR and sTfR-F index were 1.32 ± 0.3 mg/L (95% CI, 1.3-1.36) and 0.9 ± 0.25 (95% CI, 0.87-0.93). The reference intervals were 0.84 to 1.97 mg/L and 0.51 to 1.44, respectively. sTfR and sTfR-F index values were significantly higher in boys (1.39 ± 0.3 vs. 1.23 ± 0.26 mg/L, P<0.0001 and 0.93 ± 0.37 vs. 0.86 ± 0.22, P<0.04) and decreased with age (P<0.0001 and 0.04, respectively). No changes were recorded in erythropoietin. Age, sex, pubertal status, and ferritin predicted 24.1% of sTfR variability and age, sex, pubertal status, transferrin saturation, rHb, erythrocytes, and reticulocytes predicted 15% of sTfR-F index variability.

Ovarian juvenile granulosa cell tumors in infants.

Juvenile ovarian granulosa cell tumors (JGCTs) are described infrequently in pediatrics, and their finding in prepubertal patients is exceptional. Most of the tumors are benign, but recurrences up to 4 years of follow-up have been described. We present 2 cases of JGCT in infants: 1 with late recurrence of bilateral ovarian JGCT and 1 in a newborn with Ollier disease. Clinical diagnosis and treatment of JGCT are revised.